Synthesis of Enantiomerically Enriched 1,2,3- Triazole-derivatized Homoalanines

Abstract

In recent decades, the synthesis of amino acid –
triazole conjugates has become an emerging area. L- and Dazidohomoalanine
derivatives readily undergo copper(I)-
catalyzed azide-alkyne dipolar cycloaddition reaction. The
expected 4-substituted-1H-1,2,3-triazol-1-yl-homoalanines are
obtained in the reactions of either N- and O-protected or
protecting-group-free azidohomoalanines with various alkynes.
1,2,3-Triazole conjugate formation tolerates various functional
groups. The synthetic approach that uses N- and O-protected
starting materials relays on the standard chromatographic
purification of intermediates that are further deprotected by
hydrogenolysis. In this way, the purification of final products is
not required. The synthetic approach that uses protecting-groupfree
azidohomoalanine is faster from a synthetic point of view as
it includes only one step. However, the purification of protectinggroup-
free amino acid derivatives is laborious. Additionally, we
have shown that the chiral stationary phase CROWNPAK® CR(+),
which is based on chiral crown ether as a selector, is applicable
for direct chromatographic determination of enantiomeric ratio
of the title products.